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白藜芦醇对糖尿病大鼠肾皮质氧化应激损伤的保护作用 被引量:7

Protective effects of resveratrol on the oxidative stress injuries in renal cortex of diabetic rats with nephropathy
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摘要 目的探讨白藜芦醇对糖尿病大鼠肾皮质蛋白烟酰胺腺嘌呤二核苷酸磷酸氧化酶4(NOX4)、葡萄糖调节蛋白78(GRP78)表达的影响,以研究白藜芦醇对糖尿病大鼠肾皮质氧化应激损伤的保护作用。方法将15只SD雄性大鼠应用链脲佐菌素(STZ)制造糖尿病大鼠模型。13周后将造模成功的12只大鼠随机分为糖尿病组(DM组,n=6)和白藜芦醇干预组(DR,n=6),以6只健康sD大鼠作为对照组(NC组)。DR组大鼠给予白藜芦醇10mg·kg^-1·d^-1每日固定时间连续灌胃2周,DM组用等体积0.5%羧甲基纤维素钠溶液灌胃,至第14周结束。第14周结束时,检测3组大鼠的血糖、体重、血肌酐、血尿素氮、24h尿微量白蛋白。取肾组织,制石蜡切片做PAS染色观察肾小球肾小管形态学变化。取10%肾皮质组织匀浆后测定丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平。Westernblotting法检测肾皮质NOX4和GRP78蛋白表达的改变。结果与NC组相比,DM组大鼠血糖、血肌酐、血尿素氮、24h尿微量白蛋白均显著升高(t=-52.324、-20.487、-20.724、-55.476,均P〈0.0167),而体重则明显下降(t=5.820,P〈0.0167);白藜芦醇干预后,DR组大鼠24h尿微量白蛋白、血肌酐、血尿素氮均比DM组呈好转趋势(t=13.963、7.849、8.678,均P〈0.0167);而DR组体重和血糖与DM组相比差异无统计学意义(t=-1.767、1.876,均P〉0.0167)。与NC组相比,DM组MDA水平明显增加(t=-10.661,P〈0.0167),而SOD、CAT水平降低(t=8.124、8.222,均P〈0.0167);而与DM组相比,DR组SOD水平升高(t=-12.309,P〈0.0167),MDA水平降低(t=4.475,P〈0.0167),2组CAT活力差异无统计学意义(t=-3.029,P〉0.0167)。肾脏组织PAS染色显示NC组大鼠基底膜完整无增厚,DM组大鼠肾小球系膜基质增多,系膜细胞增生,DR组则� Objective To investigate the effect of resveratrol (Res)on the protein expression of reduced form of nicotinamide-adenine dinucleotide phosphate oxidase 4 (NOX4) and glucose-regulated protein 78 ( GRP78 ) and its protective effects on the oxidative stress injuries in the renal cortex of diabetic rats. Methods Fifteen SD rats were given a single intraperitoneal injection of streptozotocin(STZ) to set up animal models of diabetes. Twelve weeks after STZ injection, 12 rat diabetes models were established successfully and were randomized into diabetes mellitus group ( group DM, n = 6 ) and Res intervention group ( group DR, n = 6). Another 6 untreated healthy SD rats served as normal control ( group NC). Rats in DR group were administered intragastricly with Res 10 mg ·kg^-1 · d^-1 while those in DM group withequal volume of 0. 5% sodium carboxymethylcellulose regularly for 2 weeks. At the end of the experiments, the blood glucose (BG), body weight (BW), serum ereatinine (Ser), blood urea nitrogen (BUN), 24 urinary albumin excretion(UAE) of all rats were measured. Renal eortex from the groups were embedded in paraffin and sectioned for morphological studies. The activity of malondialdehyde (MDA), superoxide dismutase (SOD) and eatalase (CAT) in the renal cortex was assayed by chromatometry. The expression of NOX4 and GRP78 proteins in the renal cortex were deteeted by using Western blotting. Results Compared with those in group NC, the BW in group DM deereased, while BG, Scr, BUN and 24h UAE increased signifcantly(t= - 52. 324, - 20. 487, - 20. 724, - 55. 476, all P 〈 0. 0167). It indicated that resveratrol improved the 24 h UAE, Scr and BUN in group DR as compared with those in group DM ( t = 13. 963, 7. 849, 8. 678, all P 〈0. 0167) ; but there was no significant differences in BG and BW between the two groups( t = - 1. 767, 1. 876, all P 〉 0. 0167 ). Moreover, the MDA activity in DM group increased while the SOD and CAT activity decreas
出处 《中华糖尿病杂志》 CAS 2012年第4期229-233,共5页 CHINESE JOURNAL OF DIABETES MELLITUS
关键词 糖尿病肾病 白藜芦醇 氧化应激 内质网应激 大鼠 Diabetic nephropathies Resveratrol Oxidative stress Endoplasmic reticulumstress Rats
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